Agenus Inc. announced expanded data from the company's phase 1b study of botensilimab (BOT, multifunctional immune activator) in combination with balstilimab (BAL, anti-PD-1) in patients with advanced sarcomas. The results were presented in an oral presentation at the European Society for Medical Oncology (ESMO) Congress 2023. Relapsed/refractory sarcoma represents a significant unmet medical need where existing standard of care options and previous immunotherapies have shown limited activity.

At present, available treatments for advanced soft tissue sarcoma patients only have modest activity. The sarcoma cohort presented is part of a larger phase 1b study evaluating the safety, efficacy, and dose optimization of BOT alone and in combination with BAL in multiple advanced solid tumors. Study Design and Highlights: A total of 41 evaluable patients received either 1 or 2 mg/kg BOT every 6 weeks and 3 mg/kg BAL every 2 weeks.

Patient Demographics: Majority of patients had either angiosarcoma (29%) or leiomyosarcoma (39%) subtypes; Patients were heavily pre-treated, with a median of three prior lines of therapy, including 16% who received prior PD-(L)1 therapy; Majority of patients had biomarkers associated with poor response to immunotherapy: 87% had a low tumor mutation burden (Efficacy in all comers (as measured by iRECIST; n=41); 40% 6-month PFS; 20% ORR; 29% ORR at the BOT 2 mg/kg dose level; 15% ORR at the 1 mg/kg dose level; 63% disease control rate (best response of a complete response + partial response + stable disease); Median duration of response was 19.4 months; Safety in all comers (N=50); No new safety signals reported, with tolerability consistent across tumor types; Adverse events were generally manageable and reversible; Diarrhea/colitis was the most clinically significant immune-mediated adverse event; No grade 4 or 5 treatment-related adverse events and no related cases of irreversible events such as hypophysitis, pneumonitis, hepatitis, or myocarditis were reported.